Authors: Ebru Aras, Giorgio Ramadori, Kenichiro Kinouchi, Yu Liu, Rafael M. Ioris, Xavier Brenachot, Sanda Ljubicic, Christelle Veyrat-Durebex, Silvia Mannucci, Mirco Galié, Pierre Baldi, Paolo Sassone-Corsi, Roberto Coppari
Summary: Loss of synchrony between geophysical time and insulin action predisposes to metabolic diseases. Yet the brain and peripheral pathways linking proper insulin effect to diurnal changes in light-dark and feeding-fasting inputs are poorly understood. Here, we show that the insulin sensitivity of several metabolically relevant tissues fluctuates during the 24 h period. For example, in mice, the insulin sensitivity of skeletal muscle, liver, and adipose tissue is lowest during the light period. Mechanistically, by performing loss- and gain-of-light-action and food-restriction experiments, we demonstrate that SIRT1 in steroidogenic factor 1 (SF1) neurons of the ventromedial hypothalamic nucleus (VMH) convey photic inputs to entrain the biochemical and metabolic action of insulin in skeletal muscle. These findings uncover a critical light-SF1-neuron-skeletal-muscle axis that acts to finely tune diurnal changes in insulin sensitivity and reveal a light regulatory mechanism of skeletal muscle function.
Source: Cell Reports, 2019; 27 (8): 2385